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Wellcome Building Sessions 1

Session 1：Enzymes as Primary Points of Drug Action＆Chairman：F．BERGEL 1

Chairman＇s introduction 1

Inhibition of acetylcholinesterase＆by I．B．WILSON 4

Discussion：ALDRIDGE，BECKETT，BERGEL，BLASCHKO，KREBS，R．J．P．WILLIAMS，WILSON 13

Carbonic anhydrase inhibition and physiological function＆by H．W．DAVENPORT 16

Discussion：BERGEL，BLAIR，DAVENPORT，HUNT，LUTWAK-MANN，R．J．P．WILLIAMS 27

Session 2：Active Transport＆Chairman：W．WILBRANDT 30

Pinocytosis＆by H．HOLTER 30

Discussion：GOLBERG，HOLTER，SOLS，YOUNG 39

Possible mechanisms of active transport＆by W．WILERANDT 43

Discussion：HOLTER，SMYTH，WIDDAS，WILBRANDT 57

Effects of drugs on active transport＆by K．H．BEYER and J．E．BAER 60

Discussion：BEYER，WILBRANDT 82

Session 3：Multiple Mechanisms＆Chairman：J．H．GADDUM 83

Ⅰ．Insulin 83

The explanation of the action of insulin on sugar permeability at molecular level＆by R．B．FISHER 83

Action of insulin on metabolic reactions＆by E．B．CHAIN 95

Discussion：BUSH，CHAIN，DANIELLI，de DUVE，FISHER，KEYNES，MARRACK，SOLS，WILBRANDT，WOLLENBERGER，YOUNG 110

Ⅱ．Digitalis 115

Action of cardiac glycosides on ionic movements＆by M．WEATHERALL 115

Digitalis：action on metabolism and the contractile system＆by A．WOLLENBERGER 127

Discussion：BAKER，DRAPER，EDMAN，KEYNES，WASER，WHITTAM，WOLLENBERGER 150

Ⅲ．Central Nervous System Depressants 155

Action of barbiturates upon respiratory enzymes＆by W．N．ALDRIDGE 155

Appraising enzymic actions of central depressants by examining cerebral tissues＆by H．MCILWAIN 170

Discussion：ALDRIDGE，BRADLEY，CREMER，DRAPER，JOHNSON，JUDAH，KEYNES，MCILWAIN，NICOLLS，PHILLIS，REMMER，WHITTAM，R．J．P．WILLIAMS 199

Section 4：Receptors＆Chairman：W．D．M．PATON 206

Relation between enzymes and cholinergic receptors＆by P．G．WASER 206

Discussion：COLLIER，CREESE，HOBBIGER，WASER 218

Induction of receptors＆by R．MILEDI 220

Discussion：BECKETT，DORNHORST，MILEDI，PATON，PETERS，VRBOVA，ZAIMIS 236

Session 5：Altered Drug Metabolism＆Chairman：R．T．WILLIAMS 239

Chairman＇s introduction 239

Adaptive enzymes in animals＆by W．E．KNOX 245

Discussion：BERGEL，FISHER，KNOX 274

Drug tolerance＆by H．REMMER 276

Discussion：REMMER，SCHULMAN，R．T．WILLIAMS 298

The genetics of drug sensitivity with special reference to suxamethonium＆by H．HARRIS and MARY WHITTAKER 301

Discussion：AMBACHE，BLASCHKO，DANIELLI，HARRIS，HOBBIGER，KNOX，MILEDI，SPINKS 313

Session 6：Drug Metabolism：Subcellular Aspects＆Chairman：SIR RUDOLPH PETERS 317

Drug metabolism－subcellular mechanisms＆by B．B．BRODIE 317

Discussion：BECKETT，BRODIE，LACEY，NIMMO-SMITH，REMMER，R．J．P．WILLIAMS 340

Cellular injury by drugs＆by K．R．REES 344

Protection against cellular injury by drugs＆by J．D．JUDAH 359

Discussion：ATKINSON，BRODIE，DRAPER，GOLBERG，JUDAH，O＇BRIEN，PATON，REES，REMMER，WEATHERALL 384

Session 7：Panel Discussion＆Chairman：J．F．DANIELLI 388

Speakers：ALDRIDGE，BERGEL，BLASCHKO，BRODIE，de DUVE，FISHER，GADDUM，HOLTER，JUDAH，MCILWAIN，PATON，PETERS，REMMER，SHULMAN，SMYTH，SOLS，SPINKS，WASER，WEATHERALL，WILBRANDT，R．J．P．WILLIAMS，R．T．WILLIAMSS 388

Ciba Foundation Sessions on Drug-Enzyme Interaction at the Molecular level＆Chairman：SIR HANS KREBS 401

Session 1：Enzymes 401

Introduction：Enzymes＆by J．F．DANIELLI 401

Models of active centres：acetylcholine 410

Active transport 418

Mode of action of insulin 423

Limitations of enzymes as models 429

Section 2：Receptors 435

Introductions：Receptors＆by H．O．SCHILD 435

Definition of receptors 439

Identifying active centres 443

Effect of denervation on receptors 451

Events at the cell membrane 453

Rate theory of drug action 456

Interaction at the Subcellular and Cellular Levels＆Chairman：SIR RUDOLPH PETERS 463

Session 3：Subcellular Level 463

Introduction：Membranes＆by C．DE DUVE 463

Subcellular particles 472

Phosphatidic acid cycle 478

Antihistamines and membrane permeability 481

Drug concentrations in vitro 484

Session 4：Cellular Level 487

Introduction：Cellular aspects＆by H．MCILWAIN 487

Reconstituting in vitro 488

In vitro and in vivo 494

Microsomal enzymes 497

Endoplasmic reticulum 505

Enzymes in young animals 508

Transaminase and GABA 514

Drug interactions 516

General considerations 518